Case Reports
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failure or pulmonary edema are to be treated with surgical or interventional procedures before being discharged from hospital. It has been reported that covered stents can be safely used in the treatment of iatrogenic APW (1-3, 7, 8). Surgical interventions are frequently performed to treat both iatrogenic and native APW, and the potential results of surgery are well known (5). We started to follow-up our patient in the intensive care unit and initiated medical treatment. During follow-up, the patient developed congestive heart failure. The patient did not respond to intense medical treatment and underwent surgery to repair the iatrogenic APW on day 5 after balloon angioplasty. We also thought that surgery could be safer due to the large iatrogenic APW. The communication between the aorta and pulmonary artery was repaired primarily. The stenosis in the left pulmonary artery was repaired and widened using a patch. Our patient rapidly recovered from heart failure after surgery.
Conclusion
The patients in whom the LeCompte maneuver is used during arterial switch operations are at risk of development of stenosis in the pulmonary artery and its branches. After performing bal-loon angioplasty on stenosis of the branches of the pulmonary ar-tery, the rare but important complication of iatrogenic APW must be considered. Even if the surgeon is experienced in handling complications, the surgical team and operation room should be prepared for emergency interventions.
References
1. Vida VL, Biffanti R, Stellin G, Milanesi O. Iatrogenic aortopulmonary fistula occurring after pulmonary artery balloon angioplasty: a word of caution. Pediatr Cardiol 2013; 34: 1267-8.
2. Marini D, Ferraro G, Agnoletti G. Iatrogenic "aortopulmonary win-dow": percutaneous rescue closure as a bridge to surgical repair. Cardiol Young 2016; 26: 609-11.
3. Tzifa A, Papagiannis J, Qureshi S. Iatrojenic aortopulmonary win-dow after balloon dilation of the pulmonary artery stenosis follow-ing arterial switch operation. J Invasive Cardiol 2013; 25: E188-90. 4. Takayama H, Sekiguchi A, Chikada M, Noma M, Ishida R.
Aorto-pulmonary window due to balloon angioplasty after arterial switch operation. Ann Thorac Surg 2002; 73: 659-61.
5. Alsoufi B, Schlosser B, McCracken C, Kogon B, Kanter K, Border W, et al. Current Outcomes of Surgical Management of Aortopulmo-nary Window and Associated Cardiac Lesions. Ann Thorac Surg 2016; 102: 608-14.
6. Ailawadi G, Lim DS, Peeler BB, Matsumoto AH, Dake MD. Traumatic ascending aortopulmonary window following pulmonary artery stent dilatation: therapy with aortic endovascular stent graft. Pedi-atr Cardiol 2007; 28: 305-8.
7. Stamato T, Benson LN, Smallhorn JF, Freedom RM. Transcatheter closure of an aortopulmonary window with a modified double um-brella occluder system. Cathet Cardiovasc Diagn 1995; 35: 165-7. 8. Marini D, Calcagni G, Ou P, Bonnet D, Agnoletti G. Percutaneous
treatment of aorto-pulmonary window in a one year old child. Int J Cardiol 2008; 129: e91-3.
Video 1. The angiography revealed that the contrast agent passed from the aorta into the pulmonary bed at the level of the ascending aorta.
Address for Correspondence: Dr. Kahraman Yakut, Başkent Üniversitesi Tıp Fakültesi,
Çocuk Kardiyoloji Bilim Dalı, Ankara-Türkiye
Phone: +90 312 203 68 68/1382 E-mail: kahramanyakut@gmail.com
©Copyright 2018 by Turkish Society of Cardiology - Available online at www.anatoljcardiol.com
DOI:10.14744/AnatolJCardiol.2018.24704
The role of rivaroxaban in left
ventricular thrombi
Mahmoud Abdelnaby, Abdallah Almaghraby1,
Ola Abdelkarim1, Yehia Saleh2, Basma Hammad3,
Haitham Badran4
Cardiology and Angiology Unit, Department of Clinical and Experimental Internal Medicine, Medical Research Institute, University of Alexandria; Alexandria-Egypt
1Department of Cardiology, Faculty of Medicine, University of
Alexandria; Alexandria-Egypt
2Department of Internal Medicine, Michigan State University; East
Lansing, Michigan-United States of America
3Department of Cardiology, Massachusetts General Hospital;
Boston-United States of America
4Department of Cardiology, Ain Shams University; Cairo-Egypt
Introduction
Left ventricular (LV) thrombus is usually seen in patients with significantly reduced LV systolic function especially those surviving a large ST-elevation myocardial infarction (STEMI). It usually occurs when the STEMI is anterior, anterolateral or an-teroseptal with a large area of akinesia or dyskinesia involving the apex. It may occur following an inferior or a posterior STEMI with large akinetic segments in the inferior or posterior walls in rare occasions (1).
The main risk associated with LV thrombi is distal systemic embolization that usually occurs during the first 3 - 4 months after infarction (2, 3).
The main clinical consequence of thromboembolism is the occurrence of stroke, and the current guidelines do recom-mend the use of vitamin K antagonists (VKAs) as a preventive measure in patients with LV thrombus. Non-VKA direct oral anticoagulants (DOACs) are currently replacing VKA in several clinical indications, such as in patients with non-valvular atrial
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fibrillation (AF) where they were found to be either non-inferior or superior to VKAs. However, to our knowledge, there are no robust data on the use of DOACs for the treatment of LV thrombi, and all the available data are limited to individual case reports (4, 5).
We present the effect of rivaroxaban, a DOAC, in the dissolu-tion of LV thrombi in a series of patients presenting with acute coronary syndrome (ACS) and receiving dual antiplatelet therapy (DAPT) without valvular heart disease.
Case Report
We report eight cases of LV thrombi where rivaroxaban was used instead of warfarin. Some of the patients were indicated for the use of DOACs on top of AF. Written consent was obtained from all the patients for the use of the DOACs in their cases after proper explanation. Tables 1 and 2 show the demographic char-acteristics, and clinical and follow-up data.
Discussion
Rivaroxaban is one of the DOACs that act by direct inhibition of factor Xa and has been granted approval for several clinical indications, such as treatment of deep venous thrombosis, pulmonary embolism and non-valvular AF (6-8).
Table 1. Detailed data of the included cases
Case no. 1 2 3 4 5 6 7 8
Age (years) 45 40 69 52 39 46 65 60
Sex Male Male Male Male Female Male Male Female
Diabetes mellitus Yes No No No No No Yes Yes
Hypertension Yes Yes No Yes No Yes No No
Smoking No No Yes No No No No No
Presentation NSTEMI STEMI STEMI STEMI STEMI STEMI NSTEMI NSTEMI
Complications VT None AF None None None VF Shock/AF
PCI site LAD & LCX LAD* LAD* LAD* LAD* LAD* LAD & RCA LAD & RCA
Baseline EF 40% 35% 30% 35% 40% 40% 25% 30%
EDV (mL) 140 155 159 157 142 132 169 160
Creatinine clearance (mL/min.) 122 140 78 89 142 135 102 108
LV thrombus size (mm) 10x10 12x5 13x7 14x7 8x2 10x6 12x10 12x12
HAS-BLED score 2 2 2 2 1 2 2 1
Aspirin dose (mg/day) 100 100 100 100 100 100 100 100
Clopidogrel dose (mg/day) 75 75 75 75 75 75 75 75
Rivaroxaban dose (mg/day) 15 15 20 20 15 15 15 20
Follow-up EF 50% 55% 45% 50% 55% 55% 35% 50%
Follow-up thrombus Absent Absent Absent Absent Absent Absent Present Absent
*Culprit vessel.
AF - atrial fibrillation; EDV - end-diastolic volume; EF - ejection fraction; LAD - left anterior descending artery; LCX - left circumflex artery; LV - left ventricle; PCI - percutaneous coronary intervention; RCA - right coronary artery; VF - ventricular fibrillation; VT - ventricular tachycardia
Table 2. Baseline characteristics and follow-up data Baseline characteristics (n=8) Age (years) 52.1±14.4 Male sex 6 (75) STEMI 5 (63) Diabetes mellitus 6 (75) Hypertension 6 (75) Smoking 5 (63)
Family history of CAD 0 (0)
Baseline ejection fraction (%) 34±6
Valvular heart disease 0 (0)
Atrial fibrillation 3 (38) Ventricular tachycardia 1 (13) Follow-up at 3 months (n=8) Ejection fraction (%) 46±7 Persistence of thrombus 1 (13) Stroke 0 (0) Distal embolization 0 (0) Any bleeding 0 (0)
Results are shown in the number of patients (%).
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Currently, the only recommended oral anticoagulant for the treatment of LV thrombi is warfarin (VKA). There is a paucity of data on the role of DOACs in the treatment of LV thrombi except for few case reports (5, 9, 10).
In 2014, Nagamoto et al. (11) reported the successful resolution of LV thrombus in a 77-year-old male patient with old myocardial infarction after 27 days of treatment with dabigatran without thromboembolic or bleeding complications. Similarly, in 2015, Yamamoto et al. (12) reported the successful treatment of LV thrombi in two patients with old anteroseptal myocardial infarction within 2-6 weeks of treatment with dabigatran and antiplatelet drugs.
Rivaroxaban was also used for treating a case of intraventricular thrombus in Chagas disease (13) and dilated cardiomyopathy (14). Several reported cases have shown the efficacy of apixaban in cases of intraventricular thrombi without increased risk of thromboembolic or bleeding issues even when used with DAPT in patients with post-MI (15, 16).
Azizi et al. (17) described a case of post-infarction LV thrombus dissolution using a combination of DAPT plus rivaroxaban for 3 months (Fig. 1). Makrides (4) demonstrated total LV thrombus dissolution in three cases using a reduced dose of rivaroxaban 15 mg/day in a setting of ACS requiring DAPT. In patients requiring oral anticoagulation after percutaneous coronary intervention, the European Society of Cardiology (18) states that triple therapy should be limited in duration, depending on the clinical setting, thromboembolic, and bleeding risks assessed using CHA2DS2-VASc score and HAS-BLED score, respectively. The duration should depend on the individual risk for ischemic and bleeding events. The cases in our series had a HAS-BLED score of 1 - 2.
Triple therapy including a novel oral anticoagulant may have unpredictable clinical results as only a few studies addressed patients with coronary artery disease and non-valvular AF (17). In the APPRAISE-2 study, apixaban was combined with aspirin and clopidogrel in 81% of the patients and led to a significant increase in fatal and intracranial bleeding without clinical benefit
(19). In ATLAS ACS 2, low-dose rivaroxaban (2.5–5 mg two times/ day) was administered with aspirin and clopidogrel in 92% of the patients. This was associated with a 16% reduction in the composite efficacy endpoint (cardiovascular death, myocardial infarction and stroke) and a small increase in major bleedings (20). Most observational studies and meta-analyses reported embolic events in patients with LV thrombus to occur within the first 3-4 months. Based on this temporal profile, the current guidelines recommend the duration of anticoagulation therapy patients with LV thrombi to be limited to 3 months. For the cases being reported, rivaroxaban was initiated at a dose of 15-20 mg/day in addition to DAPT (acetylsalicylic acid 100 mg/day plus clopidogrel 75 mg/day) for a period of 3 months. A follow-up transthoracic echocardiography (TTE) at 3 months revealed dissolution of the LV thrombi in 7 out of 8 patients. No thromboembolic or bleeding events were experienced. This supports previous reports on the successful use of rivaroxaban along with DAPT in the treatment of LV thrombi complicating myocardial infarction. Randomized controlled trials are needed to validate the results of these encouraging observational data. A currently ongoing phase 3 clinical trial (Apixaban Versus Warfarin in Patients with LV Thrombus) is designed to assess whether apixaban is as effective as VKA for the treatment of LV thrombus after acute ST-segment elevation MI. The primary efficacy endpoint will be the presence of LV thrombus as assessed by TTE after 3 months of treatment with oral anticoagulation and secondary efficacy endpoints of clinically significant stroke or systemic embolism requiring hospitalization, major bleeding and all-cause mortality (time frame is 3 months).
In addition, it is noteworthy that the patient with residual LV thrombus underwent another TTE 3 months later revealing a complete resolution of the thrombus.
Conclusion
Rivaroxaban can be safely used in the treatment of LV thrombi without increased risk of bleeding instead of the routinely used VKA. A large-scale randomized trial is required to evaluate the benefits and risks of the use of DOACs compared with the con-ventional treatment with VKA in patients with or at high risk of LV mural thrombi, to confirm their safety and to define the optimal dosing if combined with DAPT in patients with LV thrombi com-plicating acute MI.
References
1. Weinsaft JW, Kim J, Medicherla CB, Ma CL, Codella NC, Kukar N, et al. Echocardiographic algorithm for post–myocardial infarction LV thrombus: a gatekeeper for thrombus evaluation by delayed en-hancement CMR. JACC Cardiovasc Imaging 2016; 9: 505-15. 2. Cregler LL. Antithrombotic therapy in left ventricular thrombosis
and systemic embolism. Am Heart J 1992; 123: 1110-4. [CrossRef]
Figure 1. Two-dimensional transthoracic echocardiography showing the left ventricular apical thrombus before (a) and after (b) the use of rivar-oxaban for 3 months
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3. Udell JA, Wang JT, Gladstone DJ, Tu JV. Anticoagulation after ante-rior myocardial infarction and the risk of stroke. PLoS One 2010; 5: e12150. [CrossRef]
4. Makrides CA. Resolution of left ventricular postinfarction thrombi in patients undergoing percutaneous coronary intervention using rivaroxaban in addition to dual antiplatelet therapy. BMJ Case Rep 2016; 2016.
5. Seecheran R, Seecheran V, Persad S, Seecheran NA. Rivaroxaban as an antithrombotic agent in a patient with ST-segment elevation myocardial infarction and left ventricular thrombus: a case report. J Investig Med High Impact Case Rep 2017; 5: 2324709617697991. 6. Heidbuchel H, Verhamme P, Alings M, Antz M, Hacke W, Oldgren J,
et al. European Heart Rhythm Association Practical Guide on the use of new oral anticoagulants in patients with non-valvular atrial fibrillation. Europace 2013; 15: 625-51. [CrossRef]
7. Saar JA, Maack C; European Society of Cardiology. Diagnosis and management of acute pulmonary embolism. ESC guidelines 2014. Herz 2015; 40: 1048-54. [CrossRef]
8. Kirchhof P, Benussi S, Kotecha D, Ahlsson A, Atar D, Casadei B, et al.; ESC Scientific Document Group. 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur Heart J 2016; 37: 2893-962. [CrossRef]
9. Yildirim E, Kalkan K, Ipek E, Demirelli S, Ermiş E. Successful resolu-tion of left ventricular thrombus with apixaban treatment. Interna-tional Journal of the Cardiovascular Academy 2016; 2: 57-8. [CrossRef]
10. Kaku B. Intra-cardiac thrombus resolution after anti-coagulation therapy with dabigatran in a patient with mid-ventricular obstruc-tive hypertrophic cardiomyopathy: a case report. J Med Case Rep 2013; 7: 238. [CrossRef]
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12. Yamamoto T, Konishi T, Funayama N, Kikuchi B, Hotta D, Ohori K. Resolution of Left Ventricular Thrombus after Dabigatran Therapy in Two Patients with Old Anteroseptal Myocardial Infarction. Cardiol Pharmacol 2015; 4: 152. [CrossRef]
13. Las Casas Jr AA, Las Casas AA, Borges MAF, Melo-Souza SE. Ri-varoxaban for treatment of intraventricular thrombus in Chagas dis-ease. Journal of Cardiology Cases 2016; 13: 75-7. [CrossRef]
14. Padilla Pérez M, Salas Bravo D, Garcelán Trigo JA, Vazquez Ruiz de Castroviejo E, Torres Llergo J, Lozano Cabezas C, et al. Resolution of left ventricular thrombus by rivaroxaban. Future Cardiol 2014; 10: 333-6. 15. Mano Y, Koide K, Sukegawa H, Kodaira M, Ohki T. Successful reso-lution of a left ventricular thrombus with apixaban treatment follow-ing acute myocardial infarction. Heart Vessels 2016; 31: 118-23. 16. Berry A, Brancheau D, Zughaib M. Rapid resolution of left
ventric-ular thrombus with apixaban therapy. SAGE Open Med Case Rep 2017; 5: 2050313X17745211.
17. Azizi A, Puricel S, Cook S, Brugger N. Rivaroxaban dissolves postin-farction left ventricular thrombus. Cardiovascular Medicine - Kar-diovaskuläre Medizin - Médecine Cardiovasculaire 2016; 19: 25-7. 18. Valgimigli M, Bueno H, Byrne RA, Collet JP, Costa F, Jeppsson A, et
al. 2017 ESC focused update on dual antiplatelet therapy in coro-nary artery disease developed in collaboration with EACTS. Eur J Cardiothorac Surg 2018; 53: 34-78. [CrossRef]
19. Alexander JH, Lopes RD, James S, Kilaru R, He Y, Mohan P, et al.; APPRAISE-2 Investigators. Apixaban with antiplatelet therapy after acute coronary syndrome. N Engl J Med 2011; 365: 699-708. 20. Mega JL, Braunwald E, Wiviott SD, Bassand JP, Bhatt DL, Bode C, et
al.; ATLAS ACS 2–TIMI 51 Investigators. Rivaroxaban in patients with a recent acute coronary syndrome. N Engl J Med 2012; 366: 9-19.
Address for Correspondence: Abdallah Almaghraby, MD, Department of Cardiology,
Faculty of Medicine, University of Alexandria; Khartoum Square 21524
Alexandria-Egypt Phone: 0020 122 285 16 87 E-mail: dr.maghraby@gmail.com
©Copyright 2018 by Turkish Society of Cardiology - Available online at www.anatoljcardiol.com
